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Bioinformatics . Differentially conserved amino acid positions may reflect differences in SARS-CoV-2 and SARS-CoV behaviour

tetano

Editor, Senior Moderator
Bioinformatics


. 2021 Feb 9;btab094.
doi: 10.1093/bioinformatics/btab094. Online ahead of print.
Differentially conserved amino acid positions may reflect differences in SARS-CoV-2 and SARS-CoV behaviour


Denisa Bojkova[SUP] 1 [/SUP], Jake E McGreig[SUP] 2 [/SUP], Katie-May McLaughlin[SUP] 2 [/SUP], Stuart G Masterson[SUP] 2 [/SUP], Magdalena Antczak[SUP] 2 [/SUP], Marek Widera[SUP] 3 [/SUP], Verena Kr?hling[SUP] 3 [/SUP], Sandra Ciesek[SUP] 1 4 [/SUP], Mark N Wass[SUP] 2 [/SUP], Martin Michaelis[SUP] 2 [/SUP], Jindrich Cinatl[SUP] 1 [/SUP]



Affiliations

Abstract

Motivation: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. Here, we performed a combined in-silico and cell culture comparison of SARS-CoV-2 and the closely related SARS-CoV.
Results: Many amino acid positions are differentially conserved between SARS-CoV-2 and SARS-CoV, which reflects the discrepancies in virus behaviour, i.e. more effective human-to-human transmission of SARS-CoV-2 and higher mortality associated with SARS-CoV. Variations in the S protein (mediates virus entry) were associated with differences in its interaction with ACE2 (cellular S receptor) and sensitivity to TMPRSS2 (enables virus entry via S cleavage) inhibition. Anti-ACE2 antibodies more strongly inhibited SARS-CoV than SARS-CoV-2 infection, probably due to a stronger SARS-CoV-2 S-ACE2 affinity relative to SARS-CoV S. Moreover, SARS-CoV-2 and SARS-CoV displayed differences in cell tropism. Cellular ACE2 and TMPRSS2 levels did not indicate susceptibility to SARS-CoV-2. In conclusion, we identified genomic variation between SARS-CoV-2 and SARS-CoV that may reflect the differences in their clinical and biological behaviour.
Supplementary information: Supplementary data are available at Bioinformatics online.
 
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